Mouse Anti Human huntingtin Hybridoma [NX8]

Hydrothermal time (HTT) models describe the time course of seed germination for a population of seeds under specific temperature and water potential conditions. The parameters of the HTT model are usually estimated using either a linear regression, non-linear least squares estimation or a generalized linear regression model. There are problems with these approaches, including loss of information, and censoring and lack of independence in the germination data. Model estimation may require optimization, and this can have a heavy computational burden. Here, we compare non-linear regression with survival and Bayesian methods, to estimate HTT models for germination of two clover species. All three methods estimated similar HTT model parameters with similar root mean squared errors. However, the Bayesian approach allowed (1) efficient estimation of model parameters without the need for computation-intensive methods and (2) easy comparison of HTT parameters for the two clover species. HTT models that accounted for a species effect were superior to those that did not. Inspection of credibility intervals and estimated posterior distributions for the Bayesian HTT model shows that it is credible that most HTT model parameters were different for the two clover species, and these differences were consistent with known biological differences between species in their germination behaviour.

Background: Altered cellular vesicle trafficking has been linked to the pathogenesis of Huntington's disease (HD), a fatal, inherited neurodegenerative disorder caused by mutation of the huntingtin (HTT) protein. The Rab GTPase family of proteins plays a key role in regulation of vesicle trafficking, with distinct Rabs helping specify membrane identity and mediating cellular processes including budding, motility and tethering of vesicles to their targets. In recent years several Rab GTPases-notably, Rab5 and Rab11-have been linked to the pathogenesis of neurodegenerative disorders, including HD. Objective: We investigated whether Rab8, which regulates post-Golgi vesicle trafficking, is able to improve HD-relevant phenotypes in a well-characterised model. Methods: We overexpressed Rab8 in a Drosophila model of HD testing cellular, behavioural, and molecular phenotypes. Results: We found that Rab8 overexpression ameliorated several disease-related phenotypes in fruit flies expressing a mutant HTT fragment throughout the nervous system, including neurodegeneration of photoreceptor neurons, reduced eclosion of the adult fly from the pupal case and shortened lifespan. Rab8 overexpression also normalised aberrant circadian locomotor behaviour in flies expressing mutant HTT in a specific population of neurons that regulate the circadian clock. Intriguingly, expression of Rab8 increased the accumulation of SDS-insoluble aggregated species of mutant HTT. Conclusion: Collectively, our findings demonstrate that increased Rab8 levels protect against mutant HTT toxicity and potentiate its aggregation, likely reducing the accumulation of downstream toxic soluble species.